The overall goal of the core laboratory is to provide measurements of blood and other biological samples for the assessment of folate and one carbon metabolism states. Our working hypothesis is that assessing these states is best attained by multiple measurements. These measurements are divided into a number of categories: 1) Measurement of blood vitamin levels. 2) Measurements of blood total homocysteine level, as a functional indicator of B vitamin status particularly folate (and B12) 3) Measurements of genomic DNA methylation, which provides an insight into folate (and other B vitamins) status, particularly as it relates to the C667T mutation in the MTHFR gene, and as a possible biomarker for colorectal adenoma 4) Measurements of uracil misincorporation into DNA which is an indication of a low folate (and other B vitamins) status, and as a possible biomarker for colorectal adenoma and 5) measurements of folate form distribution in cell extracts, which provides an insight of relative rates of one carbon flow into the various metabolites. The specific aims are: To use the methods which have been routinely used in our lab in samples provided by the various sites, for the determination of plasma and red blood cell folates (microbial assays), plasma vitamin B12 (radiometric assay), plasma pyridoxal 5'-phosphate (radioenzymatic assay), plasma B2 (HPLC with fluorimetric detection) and plasma homocysteine (HPLC with fluorimetric detection). To compare folate, B12, PLP, B2 and tHcy values in representative plasma samples, between our laboratory and that of Dr Per Magnum Ueland from the University of Bergen in Norway and determine common denominators, that will allow integration of data from the EPIC study with those from the US. To determine in circulating lymphocytes and colorectal biopsies, genomic DNA methylation using our newly developed method which is based on the determination of methylcytosine concentration in hydrolyzed DNA using LCMS. To determine in circulating lymphocytes and colorectal biopsies, uracil misincorporation into DNA using GCMS of hydrolyzed DNA. To determine in same colorectal biopsies folate forms distribution using our new affinity/HPLC method for the assessment of folate status in these biopsies.